The Ultimate Guide to the MTHFR Gene Mutation: Symptoms, Treatment, and Testing

MTHFR deficiency and impaired methylation may also impact existing health conditions.

Mood disorders such as depression and anxiety are among the most common conditions associated with MTHFR mutations. Low or deficient methylfolate impairs the body’s ability to produce the neurotransmitters required for a healthy mood, increasing the risk of developing anxiety and depression.

Poor neurotransmitter production has also been associated with a higher prevalence of insomnia, adrenal fatigue and fibromyalgia in adults, and behavioral disorders in children, particularly ADHD and autism.

The gut microbiome is closely connected with the central nervous system (CNS), and the toxic accumulation of homocysteine has been implicated in Candida infections.

Vitamin B12 and folate are crucial for red blood cell production, and low levels can increase the risk of anemia. These nutritional deficiencies also result in elevated homocysteine levels, which can then lead to cardiovascular disorders such as stroke, gout, and blood clots.

Elevated homocysteine also appears to play a major role in the development of serious illnesses such as multiple sclerosis and lupus.

MTHFR is also associated with thyroid disorders such as Hashimoto’s disease(hypoactive thyroid) and Graves’ disease (hyperactive thyroid) due to a genetic susceptibility that involves shared genes and pathways affecting thyroid T cells.

Poor homocysteine regulation also appears to be prevalent in estrogen-related disorders such as polycystic ovarian syndrome (PCOS), although it may not be a direct cause. Infertility and weight gain have also been linked to estrogen and MTHFR.

Finding out whether you are affected by an MTHFR mutation may help to explain certain symptoms or health issues, such as high homocysteine or depression. This makes it possible to explore options for supplementation and other treatment.

Testing methods for identifying an MTHFR mutation include saliva tests, genetic blood test, and/or a DNA panel test.

Each method varies significantly in terms of  cost and the amount of information that can be obtained about your genetics.

More information about the pros and cons of these tests can be found in these guides:

An MTHFR mutation won’t necessarily result in the symptoms or health issues described above. Most patients with MTHFR seek treatment to correct nutritional deficiencies and/or to assist with issues such as depression, high homocysteine, or infertility.

Treating these issues requires a multi-pronged approach encompassing diet, supplementation, and lifestyle changes. In some cases, medication may be necessary.

5-MTHF/L-methylfolate

Folate (vitamin B9) is essential for healthy methylation. It is typically low in those with MTHFR mutations due to the body’s inability to activate folic acid. Supplementing with methylfolate is highly recommended as it is an active form of folate that can bypass the MTHFR genetic mutation and participate in methylation reactions.

Methylcobalamin (active vitamin B12)

B12 works alongside the enzymes that use folate to generate and utilize methyl groups, including the conversion of homocysteine to methionine.

The MTHFR genetic mutation can impair B12 absorption, and low levels of B12 are especially prevalent in those with the C677T variant.

Pyridoxal 5’-Phosphate (active vitamin B6)

Pyridoxal 5'-phosphate (P5P) is also required for the break-down of homocysteine to taurine and cysteine, hemoglobin production, and the healthy formation of the myelin sheath that surrounds and protects nerve cells.

Increase dietary intake of folate

Folate (in its natural form) is naturally present in several foods. Good sources include vegetables (especially dark leafy greens), brightly-colored fruits, nuts, seeds, beans, eggs, dairy products, beef, poultry, seafood, and grains.

Increase dietary intake of vitamin B12

Food sources of B12 include animal products such as fish, beef, poultry, eggs, milk, and other dairy products.

Those with MTHFR gene mutations must avoid folic acid. It is a synthetic form of folate used in many commercial supplements, pharmaceutical prescriptions, and fortified foods and is absorbed less well than folate and methylfolate. Those with MTHFR gene mutations lack the enzyme required to activate folic acid, which can result in the accumulation of unmetabolized folic acid.

For those with MTHFR gene mutations, certain medications should also be avoided, as well as any form of alcohol.

Homocysteine is a chemical in the blood formed when the amino acid methionine is metabolized. Vitamins B12, B6, and folate are required to recycle homocysteine back into methionine so it can be used to build other proteins.

However, deficiency in the MTHFR enzyme means that the body will also be low or deficient in 5-methyltetrahydrofolate(the active form of folate required for metabolizing homocysteine) as well asB12 and B6. As a result, homocysteine cannot be efficiently recycled and builds up the blood.

Elevated homocysteine can severely damage the lining of the arteries, increasing the risk of cardiovascular issues such as atherosclerosis (hardening of the arteries) and the development of blood clots in the arteries and veins.

High homocysteine has also been linked to other vascular disorders, including cognitive decline and dementia, mood disorders(depression, anxiety), chromosomal defects, osteoporosis, migraines, polycystic ovarian syndrome, and multiple sclerosis.

Reducing homocysteine levels is crucial, especially for those with MTHFR. This is best done through a combination of dietary changes and supplementation.

Folate is crucial for the healthy development of the fetus. Women with an MTHFR gene mutation who have low folate levels are at a higher risk for pregnancy complications such as preeclampsia and miscarriage. They also risk having a baby with neural tube defects, chromosomal abnormalities, or other developmental issues.

Adequate folate levels are crucial during preconception and pregnancy to ensure both pregnancy success and an unborn child’s healthy growth and development.

Women planning to start a family should know which form of folate to take before and during pregnancy, especially if they have an MTHFR mutation. They must also take the right prenatal vitamins to support their own and their baby’s health. It is also crucial that they first discuss any supplementation or dietary changes with their doctor. 

Diet plays a major role in supporting good health, and the right foods can help to maintain important nutrient levels.

Those with MTHFR are encouraged to follow an MTHFR treatment diet that may help reduce the risk of MTHFR-related diseases and conditions. Eating the right foods is particularly important for vegans and those with allergies or gluten sensitivities.

Although food cannot provide the same folate levels as a supplement, folate-rich foods can help support the methylation cycle. There are also plenty of foods that provide valuable vitamins and minerals that assist in managing homocysteine levels and overall good health.

As mentioned previously, those with MTHFR gene mutations are at a higher risk of deficiencies in folate and vitamin B12: two of the most crucial nutrients involved in proper methylation.

The most effective way to restore and maintain healthy levels of these vitamins is through supplementation. This is especially important for women who are pregnant or planning a pregnancy.

The first thing to understand when choosing a supplement is the difference between folic acid and methylfolate. Options for supplementation may include taking a medical food such as Deplin or an OTC multivitamin that contains methylfolate.

Methylfolate dosage will vary from person to person, so it’s highly recommended to discuss this with a health professional. Dosage will also affect how long it takes for methylfolate to work.

Supplementing with a natural form of vitamin B12—as opposed to cyanocobalamin—may also contribute to better health outcomes.

Other supplements such as S-Adenosylmethionine (SAMe) and N-Acetylcysteine (NAC) may benefit those with MTHFR when taken alongside methylfolate and B12.

A good place to start is with the Methyl-Life® product range, which has been designed specifically for those with MTHFR gene mutations. This comprehensive range includes clinically tested methylfolate and Vitamin B12, available as separate supplements or as part of multivitamin formulas. Methyl-Life® also offers a variety of other nutrients shown to support cognitive function, energy production, mood, and more.